Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration

Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is commonly associated with excitotoxicity, oxidative stress, and neuroinflammation. The pathological process of neurotoxicity induces neuronal death, interrupts synaptic plasticity in the brain, and is similar to that of diverse neurodegener-ative diseases. Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes. Specifically, brain-derived neurotropic factor (BDNF) and gamma-aminobutyric acid (GABA)-ergic transmission are related to both neurodegeneration and neuroregeneration. This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission, their underlying mechanisms, and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration. This review will provide a comprehensive over-view of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.     

SGLT2 inhibitors and incretin agents: Associations with alanine aminotransferase activity in type 2 diabetes

Aim

The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group.

Digital interventions for reducing alcohol use in general populations: An updated systematic review and meta-analysis

This article updates a 2017 review on the effectiveness of digital interventions for reducing alcohol use in the general population. An updated systematic search of the MEDLINE database was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify randomized controlled trials (RCTs) published from January 2017 to June 2022 that evaluated the effectiveness of digital interventions compared with no interventions, minimal interventions, and face-to-face interventions aimed at reducing alcohol use in the general population and, that also reported changes in alcohol use (quantity, frequency, quantity per drinking day, heavy episodic drinking (HED), or alcohol use disorders identification test (AUDIT) scores). A secondary analysis was performed that analyzed data from RCTs conducted in students. The review was not preregistered. The search produced 2224 articles. A total of 80 studies were included in the review, 35 of which were published after the last systematic review. A total of 66, 20, 18, 26, and 9 studies assessed the impact of digital interventions on alcohol quantity, frequency, quantity per drinking day, HED, and AUDIT scores, respectively. Individuals randomized to the digital interventions drank 4.12 (95% confidence interval (CI): 2.88, 5.36) fewer grams of alcohol per day, had 0.17 (95% CI 0.06, 0.29) fewer drinking days per week, drank approximately 3.89 (95% CI: 0.40, 7.38) fewer grams of alcohol per drinking day, had 1.11 (95% CI: 0.32, 1.91) fewer HED occasions per month, and had an AUDIT score 3.04 points lower (95% CI: 2.23, 3.85) than individuals randomized to the control condition. Significant reductions in alcohol quantity, frequency, and HED, but not quantity per drinking day, were observed among students. Digital interventions show potential for reducing alcohol use in general populations and could be used widely at the population level to reduce alcohol-attributable harms.     

Expedition of liposomes to intracellular targets in solid tumors after intravenous administration

Liposomes as a drug delivery system provides a leading approach for the systemic (intravenous) administration of drugs. Several approaches to kill tumor cells specifically have been developed, but still there is dearth in their selectivity. Among all other nano-carrier systems, liposomal formulations of cytotoxic drugs have received an appreciable recommendation in the form of clinical approvals. Liposomal delivery provides the benefits of reduced toxicity and enhanced efficacy for the treatment of cancer. However, delivery of liposomes to desired cell type with its further trafficking to desired intracellular organelle is a challenging, yet a promising approach for safer cancer therapeutics. Several anatomical-physiological barriers starting from systemic to cellular to intracellular levels are required to be overcome to achieve efficient cancer therapy. This review discusses the barriers associated with the delivery of liposomes from the extracellular to intracellular compartments of a solid tumor and further summarizes the development of liposomal carrier system to overcome these barriers.     

Generalized eruptive histiocytoma. A case report with a review of the literature.

A case of generalized eruptive histiocytoma in a 52-year-old Indian male is described. This is probably the tenth case in the world and the first from this country. Histopathological features are discussed in detail and the literature is reviewed.     

Survival in untreated early stage non-small cell lung cancer

BACKGROUND: The aim of this study was to determine the survival of untreated stage I and II in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A retrospective analysis of medical charts of all patients diagnosed with early stage NSCLC, between January 1990 and December 2001, was conducted and patients who were not treated were identified. Data on patient's age, gender, stage of the disease, pathology, reason for non-treatment and cause of death were reviewed. RESULTS: Thirty-nine patients with untreated stage I and II NSCLC were identified. The median age at diagnosis was 77 years; 66.7% were men and 33.3% were women. All patients were Caucasian and 66.7% had stage I disease, 46.2% had squamous cell carcinoma, while adenocarcinoma was found in 28.2%. The major reason for non treatment was chronic obstructive pulmonary disease (64.1%) and the main cause of death was metastatic disease (48.7%). The overall mean survival was 11.9 months. The mean survival at stage I was not statistically different from the mean survival at stage II (13.7 months vs. 8.4 months) (p < 0.12). CONCLUSION: Patients with untreated early stages NSCLC have a very poor prognosis. Alternative therapies that are better tolerated should be investigated in these patients with early stage NSCLC who cannot be offered standard treatment.